It has been suggested that prenatal cocaine exposure exerts its effect on neurobehavioral development through impaired frontal cortical development (Rando et al., Biol. Psychiatry 74:482-489, 2013; Roussotte et al., J. Neurodev. Disord. 4:22, 2012); however, elucidation of these effects in human subjects is fraught with difficulties related to numerous confounding variables such as multi-drug usage, nutrient intake, environmental factors (Ackerman et al., Pediatrics 125:554-565, 2010), and, potentially, genetic differences. Importantly, the underlying mechanisms defining the relationship between genetic factors and varying responses to cocaine are not known. It has previously been demonstrated that, in rats, prenatal cocaine exposure during the most active period of neural progenitor proliferation induces cytoarchitectural changes in the embryonic neocortex (Lee et al., Synapse 65:21-34, 2011). These cytoarchitectural changes are initiated by N-oxidative metabolism of cocaine and consequent oxidative ER stress signaling (Lee et al., PLoS Med. 5:e117, 2008). However, due to the significant differences between humans and rodents in neocorticogenesis (Rakic, Nat. Rev. Neurosci. 10:724-735, 2009) and CYP-mediated drug metabolism (Martignoni et al., Expert Opin. Drug Metab. Toxicol. 2:875-894, 2006) it has been difficult to translate these findings from the rodent model directly to human development.